We propose to investigate the areas deemed most promising for providing an integrated synthesis of the fundamental mechanisms of hypertension. We regard the following constellation of factors: 1) renal humoral agents and renal handling of Na; 2) body Na, ECF and blood volume; 3) cardiac output; 4) brain control of Na, volume, and the circulation as an interrelated axis affecting 5) the caliber of peripheral resistance vessels in normotension and hypertension. All projects will attempt to gain more knowledge concerning this constellation. We will study: a) a circulating humoral vasoconstrictive agent in hypertensive Dahl "S" rats, as to its cause, identity, and source; b) a humoral anti-natriuretic agent in "S" rats; c) the relationship of specific brain areas to Dahl hypertension and to natriuresis; d) body Na in Dahl rats after 3 days of salt feeding; 3) the effect of beta-blockers on Dahl hypertension; f) PGE2 and PGF2alpha in quick-frozen Dahl papillas and in Dahl urine will be compared; g) PGH2 will be infused into kidneys to prevent the full rise in papillary Na after indomethacin; h) Can chronic thiazide shift the pressure natriuresis curve in "S" rats? i) Is papillary Na diminished in hypertensive "S" rats?